Arteriole hyalinosis was visible. Glomerular basal membrane thickening and mesangial expansion was also present with interstitial fibrosis, lymphocytic infiltration, and tubular atrophy. Immunofluorescence revealed linear IgG deposit and albumin in the glomerular basement membrane. Electron microscopy wasn't performed.

Histological integration with clinical and laboratory information confirmed the diagnosis of atheroembolic renal disease, with the most likely trigger being the start of hypocoagulation, seven months earlier.

The patient discontinued hypocoagulation with rivaroxaban and optimized therapy for the control of several cardiovascular risk factors.

Another hypotensive was associated and an oral antidiabetic drug, an HMG co‑A reductase inhibitor and an antiplatelet aggregator agent were initiated. However, the patient evolved with progressive deterioration of renal function, with severe azotemia and with no evidence of recovery. He needed to start dialysis therapy in hospital, with subsequent integration in a chronic hemodialysis program.

DISCUSSION AND CONCLUSION

Atheroembolic renal disease, due to its nonspecific clinical presentation, is an under‑recognized pathology.^1,2 Its diagnosis is dependent on a high degree of clinical suspicion, with a focus on a detailed anamnesis and physical examination. In the coming years, its incidence is expected to increase, not only due to the greater longevity of patients with diffuse atherosclerosis, but also to a greater number of invasive vascular procedures and the widespread use of anticoagulants and fibrinolytics in clinical practice.^2,3

Atheroembolic renal disease has a classic triad that combines the presence of acute or subacute renal injury with signs of peripheral embolization and exposure to a triggering event. When present, this triad establishes the diagnosis itself, eliminating the need for additional histological evaluation.^1,2,5 In the present case, there was no sign of involvement of other organs, with only nonspecific constitutional symptoms of asthenia, anorexia and unquantified weight loss, without objectifying the typical findings of peripheral involvement. Given the absence of vascular manipulation and assuming the scarcity of bibliography on atheroembolic renal disease associated with new oral anticoagulants (including rivaroxabano), percutaneous kidney biopsy proved to be essential.

In atheroembolic renal disease, and similarly to what was seen in the present case, histological findings illustrate the occlusion of small and medium‑sized arteries by cholesterol crystals from atherosclerotic plaques.^5,6 Once constituted, these crystals indicate a cellular inflammatory reaction, with diffuse endothelial proliferation and subsequent fibrosis. Needle‑shaped cholesterol crystals within the vessel lumen are pathognomonic and, as the present case, it permits the diagnosis of atheroembolic renal disease, distinguishing this from nephroangiosclerosis or other pathologies.⁷ The arteriole hyalinosis, the glomerular basal membrane thickening and the presence of linear IgG deposit and albumin in the immunofluorescence lead to the suspicion of a diagnosis of diabetic kidney disease. In spite of there being no previous history known of diabetes mellitus, there are registers of hyperglycemia with HbA1c upper 6.5% at hospital admission.

Once there is no specific treatment, therapy should focus on the intensive control of cardiovascular risk factors and, whenever possible, avoidance of potential precipitating events. HMG co‑A reductase inhibitors appear to be one of the most beneficial drugs in primary prevention, probably due to their stabilizing role in atherosclerotic plaques through lipid control and anti‑inflammatory effect. The use of antiplatelet agents is controversial and strongly dependent on the need for secondary prevention.^4,6

The poor prognosis of this disease reflects the severity of the underlying vascular pathology. Approximately 30% of patients, as in the present case, go on to need renal function replacement therapy.³

Cholesterol crystal embolisms have been described in association with the use of various anti‑thrombotic drugs, and this complication can occur several weeks after the start of these drugs.⁸ In spite of the fact that cholesterol crystal embolisms can also be spontaneous, in the present case the authors consider that a coincident (and non‑relational) effect with the start of the drug cannot be excluded.

The association of atheroembolic renal disease with the start of hypocoagulation is currently described in about 7% of iatrogenic reports.^1,2 The contribution of new oral anticoagulants, probably due to their more recent use, isn't yet fully defined; the hypothesis of a lower risk of kidney injury associated with these has been raised when compared with vitamin K antagonists. However further studies are needed.⁹

In 2018, Muller‑Hansma et al. presented two reports of cholesterol crystal embolisms associated with the use of an oral anticoagulant, received by Netherlands Pharmacovigilance Centre Lareb. One of these concerned an 80‑year‑old male, with medical history of aortic graft surgery, myocardial infarction treated with coronary angioplasty, multiple transient ischemic attacks and atrophy of the left kidney, who presented an atheroembolic renal disease about one week after starting oral anticoagulant (initially treatment with dabigatran and after 5 days replacement by edoxaban) for atrial fibrillation. The second case concerned a 71‑year‑old male with many cardiovascular risk factors, with diagnosis of atheroembolic renal disease about 5 weeks after administration of rivaroxaban for atrial fibrillation.¹⁰

The authors underline that although the time after initiation of the drug (7 months) described in the present case is not the most typical interval, a possible relationship exists between rivaroxaban and the diagnosis of atheroembolic renal disease. They emphasize that to date there are few described cases of this renal disease associated with hypocoagulation with rivaroxaban, justifying the relevance of this report.

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